Prolonged experimental CD4+ T-cell depletion does not cause disease progression in SIV-infected African green monkeys

CD4+ T-cell depletion is a hallmark of HIV infection, leading to impairment of cellular immunity and opportunistic infections, but its contribution to SIV/HIV-associated gut dysfunction is unknown. Chronically SIV-infected African Green Monkeys (AGMs) partially recover mucosal CD4+ T-cells, maintain gut integrity and do not progress to AIDS. Here we assess the impact of prolonged, antibody-mediated CD4 + T-cell depletion on gut integrity and natural history of SIV infection in AGMs. All circulating CD4+ T-cells and >90% of mucosal CD4+ T-cells are depleted. Plasma viral loads and cell-associated viral RNA in tissues are lower in CD4+-cell-depleted animals. CD4+-cell-depleted AGMs maintain gut integrity, control immune activation and do not progress to AIDS. We thus conclude that CD4+ T-cell depletion is not a determinant of SIV-related gut dysfunction, when gastrointestinal tract epithelial damage and inflammation are absent, suggesting that disease progression and resistance to AIDS are independent of CD4+ T-cell restoration in SIVagm-infected AGMs.


Field-specific reporting
Please select the one below that is the best fit for your research. If you are not sure, read the appropriate sections before making your selection.

Life sciences
Behavioural & social sciences Ecological, evolutionary & environmental sciences For a reference copy of the document with all sections, see nature.com/documents/nr-reporting-summary-flat.pdf

Life sciences study design
All studies must disclose on these points even when the disclosure is negative.  JCI, 2018;Schechter et al., Sci Transl. Med, 2017;Pandrea, JVI 2008;Pandrea, JVI 2006), we were able to detect significant differences in the main parameters investigated here with similar or even lower experimental group sizes.
No data was excluded during this study but data are missing for some timepoints, either due to a lack of tissues (for IHC and PCR assays) or due to an insufficient number of cells (for flow cytometry experiments).
Due to high costs and the fact that all assays were done on all 12 animals, we have not performed replication analysis. However, we have used reagents that have been widely used in the field. Moreover, we had values at baseline (for CD4 T cells, viral loads and levels of inflammation) that were in the range of what was previously reported for SIVsab-infected AGMs in the literature. Longitudinal samples were used for this study. We compared study animals with themselves and with control animals, over the entire followup. When evaluating inflammation, gut integrity, immune activation, at least 2 different techniques were used. For biomarkers, when possible, samples from the same animal were tested in the same round to limit inter-batch variation. For PCR assays (viral load, cell-associated viral RNA and DNA), samples were tested in duplicate.
Those animals were not randomly allocated, but before initiating CD4-depleting antibody, plasma viral loads were quantified to verify that all animals were within the same range.
No, investigators were not blinded during data acquisition or analysis. As all lab members are involved in cell separation and preparation of the dilutions of the CD4-depleting antibody, it was not feasible to keep everyone blinded as the lymphocytes numbers were drastically different between the 2 groups. The person running the PCR assays was not involved in cell separation, and was thus kept blinded.
We require information from authors about some types of materials, experimental systems and methods used in many studies. Here, indicate whether each material, system or method listed is relevant to your study. If you are not sure if a list item applies to your research, read the appropriate section before selecting a response. Note that full information on the approval of the study protocol must also be provided in the manuscript.
The following antibodies were used to determine the absolute cell counts in peripheral blood, with Trucount tubes: CD45 ( Twelve African green monkeys were included in this study. Those AGMs were all adult males. The animals' age was determined by the veterinarians based on phenotypic criteria.

N/A
Sex was not considered in our study design, as sex is not known to have a major impact on CD4+ T-cell levels (Pandrea I et